Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies

NCT ID: NCT05397496

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-03
• Study Completion Date: 2028-06-05

Brief Summary

This is an open-label, multicenter, phase I study, which primary objective is to characterize the safety and tolerability of PIT565 and to identify maximal tolerated doses (MTDs) and/or recommended doses (RDs), schedule and route of administration in relapsed and/or refractory B-cell Non-Hodgkin lymphoma (R/R B-NHL) and relapsed and/or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

Detailed Description

This is an open-label, multicenter, phase I study of PIT565 in patients with R/R B-NHL and R/R B-ALL.

The study comprises a dose escalation part of PIT565 in two independent groups (group A: R/R B-NHL and B: R/R B-ALL) and a dose expansion part in three independent groups (R/R large B-cell lymphoma (LBCL) randomized in 1:1 ratio to two RDs (A1 and A2), and R/R B-ALL (B1)).

During the dose escalation, the safety (including the dose-dose limiting toxicity (DLT) relationship) and tolerability of PIT565 will be assessed, and schedule(s), route(s) of administration and dose(s) will be identified for use in the expansion part based on the review of these data. The RD will also be guided by the available information on pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity. The dose escalation will be guided by an adaptive Bayesian logistic regression model (BLRM) following the Escalation with Overdose Control (EWOC) principle.

Different schedules and routes of administrations will be explored in the dose escalation groups.

The dose expansion will further explore the MTD(s) and/or RD(s) and the selected schedule(s) and route of administration(s) in the three patients' groups.

Conditions

B-cell Non-Hodgkin Lymphoma (B-NHL); B-cell Acute Lymphoblastic Leukemia (B-ALL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PIT565 Group A (dose escalation part)

PIT565 in adult NHL patients for whom two or more lines of chemotherapy have failed and either having progressed (or relapsed) after autologous hematopoietic stem cell transplantation (HSCT), or being ineligible for or not consenting to the procedure

Group Type: EXPERIMENTAL

PIT565

Intervention Type: BIOLOGICAL

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

PIT565 Group B (dose escalation part)

PIT565 in adult R/R ALL patients

Group Type: EXPERIMENTAL

PIT565

Intervention Type: BIOLOGICAL

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

PIT565 Group A1 (dose expansion part)

PIT565 Recommended dose 1 (RD1) in adult R/R large B-cell lymphoma (LBCL) (DLBCL, double/triple hit High-grade B-cell lymphoma (HGBCL), Primary mediastinal large B-cell lymphoma (PMBCL), Follicular lymphoma grade 3B (FL3B)) patients

Group Type: EXPERIMENTAL

PIT565

Intervention Type: BIOLOGICAL

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

PIT565 Group A2 (dose expansion part)

PIT565 RD2 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients

Group Type: EXPERIMENTAL

PIT565

Intervention Type: BIOLOGICAL

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

PIT565 Group B1 (dose expansion part)

PIT565 in adult R/R ALL patients

Group Type: EXPERIMENTAL

PIT565

Intervention Type: BIOLOGICAL

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

Interventions

PIT565

Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study.
• Male or female patients ≥18 years of age at the date of signing the informed consent form
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2

NHL patient population

• Refractory or relapsed B-NHL
• Must have relapsed after or failed to respond to at least two prior treatment therapies including an αCD20 monoclonal antibody containing chemotherapy combination regimen
• Must have at least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan

ALL patient population

• Refractory or relapsed CD19-positive B-ALL
• Morphologic disease in the bone marrow (≥ 5% blasts)

Exclusion Criteria

• History of severe hypersensitivity to any ingredient of the study treatment or its excipients
• Contraindication to tocilizumab
• History of ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection
• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type
• Active central nervous system (CNS) involvement by malignancy or presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the 2 weeks prior to the start of study treatment
• Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur
• Patients receiving systemic treatment with any immunosuppressive medication

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Of Miami

Miami, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

The University of Kansas Clinical Research Ctr

Fairway, Kansas, United States

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

Oregon Health Sciences University

Portland, Oregon, United States

Novartis Investigative Site

Ghent, , Belgium

Novartis Investigative Site

Beijing, , China

Novartis Investigative Site

Shanghai, , China

Novartis Investigative Site

Tianjin, , China

Novartis Investigative Site

Créteil, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Rozzano, MI, Italy

Novartis Investigative Site

Reggio Emilia, RE, Italy

Novartis Investigative Site

Kashiwa, Chiba, Japan

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, , Spain

Countries

United States; Belgium; China; France; Israel; Italy; Japan; Singapore; Spain

Other Identifiers

2022-000367-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPIT565A12101

Identifier Type: -

Identifier Source: org_study_id